Oral administration of the combination with concomitant dexamethasone was shown in two pivotal studies to prevent nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy in chemotherapy-naïve patients.
Highly emetogenic chemotherapy
A randomised, double-blind study in 694 patients undergoing cisplatin-based chemotherapy for solid tumours compared three doses of netupitant (100mg, 200mg, and 300mg) plus palonosetron 500 microgram with oral palonosetron 500 microgram alone, all given as single doses on day 1. The primary efficacy endpoint was complete response (defined as no emesis and no rescue medication) for the period 0–120 hours after the start of cisplatin infusion.
At all netupitant doses, the combination produced higher complete response rates than palonosetron alone (87.4%, 87.6%, and 89.6% for netupitant 100mg, 200mg, and 300mg, respectively, vs 76.5% for palonosetron; p<0.050), with the 300mg dose showing an advantage over lower doses for all efficacy endpoints.
Moderately emetogenic chemotherapy
A second randomised, double-blind study in 1455 patients receiving moderately emetogenic (anthracycline–cyclophosphamide) chemotherapy compared a single dose of netupitant 300mg and palonosetron 500 microgram with a single dose of 500 microgram palonosetron. The primary efficacy endpoint was complete response during the delayed phase (25–120 hours after the start of chemotherapy) in cycle 1.
The percentage of patients who experienced a complete response during the delayed phase was significantly higher in the combination group than in the palonosetron-only group (76.9% vs 69.5%; p=0.001), as were the percentages in the overall (0–120 hours) and acute (0–24 hours) phases (respectively, 74.3% vs 66.6%; p=0.001 and 88.4% vs 85.0%; p=0.047).
The combination of netupitant and palonosetron was well tolerated, with a similar safety profile to that of palonosetron alone. Common adverse reactions reported were headache (3.6%), constipation (3.0%) and fatigue (1.2%).